Effects of isopulegol on pentylenetetrazol-induced convulsions in mice: possible involvement of GABAergic system and antioxidant activity

Fitoterapia. 2009 Dec;80(8):506-13. doi: 10.1016/j.fitote.2009.06.011. Epub 2009 Jun 25.


The present study investigated the effects of isopulegol, a monoterpene alcohol, in PTZ-induced convulsions and verified possible involved mechanisms. Saline, isopulegol or diazepam were intraperitonealy injected 30 min before PTZ. The latency for development of convulsions and mortality, as well as the mortality protection percentage was recorded. For investigating the involvement of GABAergic system, flumazenil was utilized. The activity of antioxidant enzyme catalase as well as the levels of reduced glutathione and lipid peroxidation were measured in brain hippocampus. Similarly to diazepam, isopulegol significantly prolonged the latency for convulsions and mortality of mice. All animals were protected against mortality at higher dose of isopulegol. Flumazenil pretreatment decreased the prolongation of seizure latency induced by both diazepam and isopulegol, although it was not able to reverse the latency and protection percent for mortality. Isopulegol also significantly prevented PTZ-induced increase in lipid peroxidation, preserved catalase activity in normal levels, and prevented the PTZ-induced loss of GSH in hippocampus of mice. These results suggest that the anticonvulsant and bioprotective effects of isopulegol against PTZ-induced convulsions are possibly related to positive modulation of benzodiazepine-sensitive GABA(A) receptors and to antioxidant properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use*
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Catalase / metabolism
  • Cyclohexane Monoterpenes
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Flumazenil / pharmacology
  • Glutathione / metabolism
  • Hippocampus / drug effects
  • Lipid Peroxidation / drug effects
  • Male
  • Mice
  • Pentylenetetrazole
  • Phytotherapy*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Receptors, GABA-A / metabolism
  • Seizures / chemically induced
  • Seizures / drug therapy*
  • Seizures / mortality
  • Terpenes / isolation & purification
  • Terpenes / pharmacology
  • Terpenes / therapeutic use*
  • gamma-Aminobutyric Acid / metabolism*


  • Anticonvulsants
  • Antioxidants
  • Cyclohexane Monoterpenes
  • Plant Extracts
  • Receptors, GABA-A
  • Terpenes
  • isopulegol
  • Flumazenil
  • gamma-Aminobutyric Acid
  • Catalase
  • Glutathione
  • Pentylenetetrazole